Miyagawa Shigeru, Kainuma Satoshi, Kawamura Takuji, Suzuki Kota, Ito Yoshito, Iseoka Hiroko, Ito Emiko, Takeda Maki, Sasai Masao, Mochizuki-Oda Noriko, Shimamoto Tomomi, Nitta Yukako, Dohi Hiromi, Watabe Tadashi, Sakata Yasushi, Toda Koichi, Sawa Yoshiki
Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
Front Cardiovasc Med. 2022 Aug 16;9:950829. doi: 10.3389/fcvm.2022.950829. eCollection 2022.
Despite major therapeutic advances, heart failure, as a non-communicable disease, remains a life-threatening disorder, with 26 million patients worldwide, causing more deaths than cancer. Therefore, novel strategies for the treatment of heart failure continue to be an important clinical need. Based on preclinical studies, allogenic human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) patches have been proposed as a potential therapeutic candidate for heart failure. We report the implantation of allogeneic hiPSC-CM patches in a patient with ischemic cardiomyopathy (ClinicalTrials.gov, #jRCT2053190081). The patches were produced under clinical-grade conditions and displayed cardiogenic phenotypes and safety (severe immunodeficient mice) without any genetic mutations in cancer-related genes. The patches were then implanted via thoracotomy into the left ventricle epicardium of the patient under immunosuppressive agents. Positron emission tomography and computed tomography confirmed the potential efficacy and did not detect tumorigenesis in either the heart or other organs. The clinical symptoms improved 6 months after surgery, without any major adverse events, suggesting that the patches were well-tolerated. Furthermore, changes in the wall motion in the transplanted site were recovered, suggesting a favorable prognosis and the potential tolerance to exercise. This study is the first report of a successful transplant of hiPSC-CMs for severe ischemic cardiomyopathy.
尽管在治疗方面取得了重大进展，但心力衰竭作为一种非传染性疾病，仍然是一种危及生命的病症，全球有2600万患者，其造成的死亡人数超过癌症。因此，治疗心力衰竭的新策略仍然是一项重要的临床需求。基于临床前研究，异体人诱导多能干细胞衍生的心肌细胞（hiPSC-CM）贴片已被提议作为心力衰竭的潜在治疗候选方案。我们报告了异体hiPSC-CM贴片在一名缺血性心肌病患者中的植入情况（ClinicalTrials.gov，#jRCT2053190081）。这些贴片是在临床级条件下生产的，表现出心脏发生表型和安全性（严重免疫缺陷小鼠），且癌症相关基因无任何基因突变。然后在免疫抑制剂的作用下，通过开胸手术将贴片植入患者的左心室心外膜。正电子发射断层扫描和计算机断层扫描证实了其潜在疗效，并且在心脏或其他器官中均未检测到肿瘤发生。术后6个月临床症状有所改善，且无任何重大不良事件，这表明贴片耐受性良好。此外，移植部位的壁运动变化得到恢复，提示预后良好且对运动具有潜在耐受性。本研究是关于严重缺血性心肌病患者成功移植hiPSC-CM的首例报告。
